Skin‐Limited Neonatal Lupus in an Infant Conceived by In Vitro Fertilization and Surrogate Gestation

ABSTRACT

Neonatal lupus erythematosus (NLE) is a rare autoimmune condition caused by the transplacental passage of maternal anti‐Ro/SSA and anti‐La/SSB antibodies, typically presenting with annular erythema or congenital heart block. We report a 3‐month‐old infant conceived by in vitro fertilization and carried by a surrogate mother who developed annular erythematous plaques in typical and atypical locations at 1 month of age. Skin biopsy and serologic testing confirmed NLE despite the absence of a known maternal autoimmune history; maternal anti‐Ro/SSA and anti‐La/SSB positivity was identified retrospectively through the surrogate's obstetrician. The cutaneous findings improved significantly with photoprotection and resolved without systemic involvement.

1. Introduction

Neonatal lupus erythematosus (NLE) is a rare condition resulting from the transplacental transfer of maternal autoantibodies, primarily anti‐Ro/SSA and anti‐La/SSB [1]. Its estimated incidence is approximately 1 in 12,500–20,000 live births, and the most frequent manifestations include annular erythematous plaques with central atrophy and congenital atrioventricular block, the latter associated with high morbidity and mortality [2, 3]. Most cases occur in infants born to mothers with known autoimmune diseases; however, it may also develop in infants of asymptomatic women who carry autoantibodies [4]. Cutaneous manifestations usually appear within the first weeks of life and tend to resolve spontaneously within the first months as the load of circulating maternal autoantibodies decreases [1]. Nevertheless, variability in clinical presentation and the absence of maternal history may delay diagnosis [3]. Reporting cases with atypical presentations contributes to expanding the understanding of the clinical spectrum of NLE and underscores the importance of a timely diagnostic approach.

2. Case Presentation

A 3‐month‐old female infant, conceived by in vitro fertilization and carried by a surrogate mother, with unknown maternal medical history, was evaluated. Pregnancy was uneventful with adequate prenatal care, and she was delivered by cesarean section at 37 weeks of gestation, with appropriate weight and length for gestational age and no perinatal complications. At 1 month of age, she developed a dermatosis characterized by annular erythematous plaques and macules with mild central atrophy, involving the scalp, periorbital region, axillae, and inguinal folds (Figure 1). The remainder of the physical examination was unremarkable, with no evidence of muscle weakness, joint abnormalities, or visceral involvement. She was initially evaluated by pediatric dermatology, where atopic dermatitis was suspected, and topical hydrocortisone was prescribed, with only partial improvement. Due to the poor response, unusual distribution, and extent of the cutaneous findings, a skin biopsy from the scalp was performed. Histopathology revealed vacuolar interface dermatitis with superficial perivascular lymphocytic infiltrate, findings consistent with NLE (Figure 2). Immunological studies showed ANA 1:160 with a fine speckled nucleolar pattern, anti‐Ro 146 (reference < 20), and anti‐La 44 (reference < 20). Other lupus‐associated autoantibodies were negative (see Table S1). Additionally, the surrogate mother's obstetrician was contacted, and maternal serology confirmed anti‐Ro/SSA and anti‐La/SSB positivity. The surrogate mother had no known history of autoimmune disease and had never undergone prior autoantibody screening. Anti‐Ro/SSA and anti‐La/SSB positivity was identified only after the infant's diagnosis, as these tests had not been part of her routine prenatal evaluation. Based on these results, the diagnosis of NLE was confirmed. Electrocardiogram and echocardiogram were normal. Additional laboratory testing was performed to assess systemic involvement. Complete blood count, renal function (serum creatinine and BUN), liver enzymes (AST, ALT), bilirubin levels, and urinalysis were all within normal limits for age. No anemia, thrombocytopenia, or hepatobiliary abnormalities were detected, and direct Coombs testing was negative. These results supported the absence of extracutaneous manifestations.

FIGURE 1.

Annular erythematous plaques involving the periorbital region (a), scalp (b), and inguinal creases (c).

FIGURE 2.

Skin biopsy demonstrating vacuolar interface dermatitis with basal layer degeneration, occasional necrotic keratinocytes, superficial lymphocytic infiltrate, and pigment incontinence, consistent with cutaneous lupus erythematosus. PAS stain, ×20. Scalp biopsy.

Management included the use of sunscreen and avoidance of sun exposure due to the risk of exacerbation of the cutaneous involvement. At 2 months' follow‐up, marked improvement was noted, with only faint annular erythematous patches on the forehead and periorbital region (Figure 3), and complete resolution of axillary and inguinal lesions.

FIGURE 3.

Follow‐up at 2 months showing marked improvement, with faint residual annular erythematous patches on the forehead and periorbital region.

3. Discussion

Neonatal lupus erythematosus (NLE) typically presents during the first weeks of life with annular erythematous plaques on the face and scalp, sometimes extending to the trunk or extremities [1]. Our patient exhibited involvement in classic sites (scalp and periorbital region) as well as less common locations such as the axillae and inguinal folds, a distribution that has been described in variant presentations of NLE and may increase diagnostic complexity [5]. This pattern highlights the importance of considering NLE when evaluating persistent or atypically distributed annular dermatoses in early infancy.

The absence of maternal autoimmune history initially lowered clinical suspicion; however, serologic testing ultimately revealed anti‐Ro/SSA and anti‐La/SSB positivity in both the infant and the surrogate mother. Similar reports describe that NLE may occur in infants born to asymptomatic women with unrecognized autoantibody positivity [4, 6]. Diagnostic delays are more likely in the context of assisted reproduction or gestational surrogacy, where maternal medical information may be limited or incomplete.

Several published reports describe NLE in infants born to asymptomatic mothers, reinforcing that unrecognized anti‐Ro/SSA and anti‐La/SSB positivity is not uncommon. Zdraveska et al. described a 3‐week‐old newborn with annular hypopigmented lesions on the face and trunk, initially misdiagnosed as tinea, whose mother was subsequently found to be autoantibody‐positive only after the infant's evaluation [7]. Intertriginous involvement has been reported in NLE, including lesions affecting the inguinal folds [8], supporting that cutaneous manifestations may extend beyond the typical sun‐exposed areas.

However, to our knowledge, reports of cutaneous NLE in the context of assisted reproduction and gestational surrogacy are exceedingly rare. A single informative case has been described in an infant conceived through in vitro fertilization and carried by a surrogate mother with known Sjögren syndrome and documented anti‐Ro/SSA and anti‐La/SSB positivity, highlighting that direct genetic inheritance is not required for NLE [9]. In contrast, in our case, the surrogate mother was asymptomatic and her autoantibody status was unknown at the time of presentation, leading to delayed recognition and diagnostic uncertainty. This distinction underscores a unique gap in maternal–infant medical information transfer in surrogacy settings.

At present, routine screening for anti‐Ro/SSA and anti‐La/SSB antibodies is not recommended in the absence of maternal autoimmune disease [10]. In this context, incomplete or fragmented maternal medical information may delay risk recognition and limit appropriate fetal stratification. Our case illustrates how such gaps can contribute to diagnostic delay when maternal autoimmune status is unknown. We suggest considering autoantibody screening in gestational surrogates to enable targeted fetal surveillance and support timely clinical decision‐making.

Reports of cutaneous NLE involving sun‐protected skin, such as the diaper area, further emphasize the heterogeneity of its clinical presentation [11]. Similar to previously described cases of annular and erosive diaper‐area plaques that initially mimicked common dermatoses [12], these presentations may complicate early clinical recognition. One proposed mechanism is an isotopic or isomorphic response, whereby prior local inflammation predisposes to immune complex–mediated skin injury in the presence of circulating maternal autoantibodies [12].

Although cutaneous NLE is typically self‐limited, long‐term follow‐up remains advisable given the potential for cutaneous sequelae, including telangiectasias, hypopigmentation, hyperpigmentation, and atrophic scarring [13]. In our patient, the early clinical course was favorable, consistent with the self‐limited nature of cutaneous NLE. However, available evidence suggests that individuals with a history of NLE may carry a modestly increased risk of developing autoimmune diseases later in life, despite a low absolute risk and an uncertain magnitude [14, 15]. Reports of subsequent systemic lupus erythematosus, Sjögren syndrome, and juvenile idiopathic arthritis in a minority of affected patients underscore the importance of long‐term follow‐up and anticipatory guidance, even in cases with an initially benign presentation.

Consent

Written informed consent was obtained from the patient's legal guardian for publication of the clinical details and accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table S1: Autoantibody profile of the patient.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.